A. Keith Stewart, MB, ChB: We still see a number of patients, Christina, who have what we call smoldering myeloma or early-stage disease that traditionally we haven’t treated. But there are a number of abstracts being presented at the ASH 2017 meeting where treating smoldering myeloma early has been explored. What are your thoughts on that and, particularly, if you can describe some of the work that’s being presented here?

Cristina Gasparetto, MD: I think it’s very interesting, actually. I think earlier on, the first concept of treatment of this population of patients was slowing down the progression and maybe treating them suboptimally. What we see now, a new current, maybe if we intervene sooner and more aggressively, we can impact on these patients. We can impact on the survival of these patients. I think it makes sense: less tumor burden, going aggressively, achieving a deeper response. So, I don’t necessarily say that we should treat all the smoldering myeloma, but I think the high risk, it makes sense. And particularly with the study of Dr. Mateos, very early, very premature data where she almost did a total therapy for these patients: KRd (Kyprolis, Revlimid, dexamethasone), transplant, consolidation, and then maintenance. And we do have a short follow up and all patients completed the regimen. But we see an enormous amount of patients achieving MRD, and if that will translate in survival advantage, it’s going to be very important. So, I think it’s an important message for patients with early disease.

A. Keith Stewart, MB, ChB: If you’re a community oncologist watching this, should they be treating smoldering myeloma or just waiting a little bit longer until we get better and longer follow up on these trials?

Cristina Gasparetto, MD: I would like to see longer follow up. Particularly, and I would like to see more data, clinical trials, because I’m concerned about the toxicity in these patients with an aggressive approach with a KRd. Actually, I was surprised that it was relatively manageable, but you have to take that into account.

A. Keith Stewart, MB, ChB: Let me ask Noopur. What do you think about treating smoldering myeloma in light of these new studies? A pretty aggressive treatment regimen for people who are asymptomatic with some risks of toxicity. What do you think?

Noopur Suresh Raje, MD: I certainly agree with what has been said, but I do want to highlight the fact that we redefined smoldering myeloma a little bit. We redefined, in fact, what is symptomatic multiple myeloma, and you have the SLiM criteria now where you have…

A. Keith Stewart, MB, ChB: You better describe it for people who…

Noopur Suresh Raje, MD: That’s more than 60% plasmacytosis in the bone marrow and better imaging modalities so that in the SLiM criteria, we have included MRI. If you have more than 2 focal lesions on the MRI—it does not have to be only an MRI, it could be a PET/CT scan or a CT scan—if you see bone disease on that, the last one is a serum free light-chain ratio. If you have a ratio of more than 100, these in fact become symptomatic active myeloma patients and should be treated actively. The teaching even today, despite the very encouraging data at this meeting, I think should be that smoldering myeloma is a patient population where we wait and watch. And until we see more mature data, I don’t think we would suggest treating these patients.

A. Keith Stewart, MB, ChB: Yes. That would be my bias, too. Hari, what do you think?

Parameswaran Hari, MD, MRCP, MS: I complete agree. Outside of a clinical trial, I don’t think we should be treating smoldering myeloma. The highest of the high-risk patients, as Noopur just mentioned, have been moved up into symptomatic myeloma now. So, the remaining people should only be treated on clinical trial.

A. Keith Stewart, MB, ChB: I was struck in one of the abstracts that when they screened what we thought was smoldering myeloma, about 35% of them had bone disease if you look hard enough.

Transcript Edited for Clarity

Transcript:

A. Keith Stewart, MB, ChB: We still see a number of patients, Christina, who have what we call smoldering myeloma or early-stage disease that traditionally we haven’t treated. But there are a number of abstracts being presented at the ASH 2017 meeting where treating smoldering myeloma early has been explored. What are your thoughts on that and, particularly, if you can describe some of the work that’s being presented here?

Cristina Gasparetto, MD: I think it’s very interesting, actually. I think earlier on, the first concept of treatment of this population of patients was slowing down the progression and maybe treating them suboptimally. What we see now, a new current, maybe if we intervene sooner and more aggressively, we can impact on these patients. We can impact on the survival of these patients. I think it makes sense: less tumor burden, going aggressively, achieving a deeper response. So, I don’t necessarily say that we should treat all the smoldering myeloma, but I think the high risk, it makes sense. And particularly with the study of Dr. Mateos, very early, very premature data where she almost did a total therapy for these patients: KRd (Kyprolis, Revlimid, dexamethasone), transplant, consolidation, and then maintenance. And we do have a short follow up and all patients completed the regimen. But we see an enormous amount of patients achieving MRD, and if that will translate in survival advantage, it’s going to be very important. So, I think it’s an important message for patients with early disease.

A. Keith Stewart, MB, ChB: If you’re a community oncologist watching this, should they be treating smoldering myeloma or just waiting a little bit longer until we get better and longer follow up on these trials?

Cristina Gasparetto, MD: I would like to see longer follow up. Particularly, and I would like to see more data, clinical trials, because I’m concerned about the toxicity in these patients with an aggressive approach with a KRd. Actually, I was surprised that it was relatively manageable, but you have to take that into account.

A. Keith Stewart, MB, ChB: Let me ask Noopur. What do you think about treating smoldering myeloma in light of these new studies? A pretty aggressive treatment regimen for people who are asymptomatic with some risks of toxicity. What do you think?

Noopur Suresh Raje, MD: I certainly agree with what has been said, but I do want to highlight the fact that we redefined smoldering myeloma a little bit. We redefined, in fact, what is symptomatic multiple myeloma, and you have the SLiM criteria now where you have…

A. Keith Stewart, MB, ChB: You better describe it for people who…

Noopur Suresh Raje, MD: That’s more than 60% plasmacytosis in the bone marrow and better imaging modalities so that in the SLiM criteria, we have included MRI. If you have more than 2 focal lesions on the MRI—it does not have to be only an MRI, it could be a PET/CT scan or a CT scan—if you see bone disease on that, the last one is a serum free light-chain ratio. If you have a ratio of more than 100, these in fact become symptomatic active myeloma patients and should be treated actively. The teaching even today, despite the very encouraging data at this meeting, I think should be that smoldering myeloma is a patient population where we wait and watch. And until we see more mature data, I don’t think we would suggest treating these patients.

A. Keith Stewart, MB, ChB: Yes. That would be my bias, too. Hari, what do you think?

Parameswaran Hari, MD, MRCP, MS: I complete agree. Outside of a clinical trial, I don’t think we should be treating smoldering myeloma. The highest of the high-risk patients, as Noopur just mentioned, have been moved up into symptomatic myeloma now. So, the remaining people should only be treated on clinical trial.

A. Keith Stewart, MB, ChB: I was struck in one of the abstracts that when they screened what we thought was smoldering myeloma, about 35% of them had bone disease if you look hard enough.